WO2020204373A2 - 고형암 진단 장치와 고형암 진단 정보 제공 방법 - Google Patents

고형암 진단 장치와 고형암 진단 정보 제공 방법 Download PDF

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WO2020204373A2
WO2020204373A2 PCT/KR2020/003158 KR2020003158W WO2020204373A2 WO 2020204373 A2 WO2020204373 A2 WO 2020204373A2 KR 2020003158 W KR2020003158 W KR 2020003158W WO 2020204373 A2 WO2020204373 A2 WO 2020204373A2
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cancer
carnitine
concentration
octanoyl
hexanoyl
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PCT/KR2020/003158
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English (en)
French (fr)
Korean (ko)
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WO2020204373A3 (ko
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유병철
김경희
박상재
우상명
이영주
이준화
최범규
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국립암센터
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Priority claimed from KR1020200024845A external-priority patent/KR102395558B1/ko
Application filed by 국립암센터 filed Critical 국립암센터
Priority to JP2021572576A priority Critical patent/JP7401121B2/ja
Priority to EP20782471.5A priority patent/EP4027139A4/en
Priority to CN202080040771.7A priority patent/CN113939737A/zh
Priority to US17/615,506 priority patent/US20220349895A1/en
Publication of WO2020204373A2 publication Critical patent/WO2020204373A2/ko
Publication of WO2020204373A3 publication Critical patent/WO2020204373A3/ko

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
    • G—PHYSICS
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    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57415—Specifically defined cancers of breast
    • G—PHYSICS
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    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
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    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
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    • G—PHYSICS
    • G01—MEASURING; TESTING
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    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57419—Specifically defined cancers of colon
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57446—Specifically defined cancers of stomach or intestine
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57484—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
    • G01N33/57488—Immunoassay; Biospecific binding assay; Materials therefor for cancer involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites involving compounds identifable in body fluids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
    • G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
    • G01N2030/8813—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
    • G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
    • G01N2030/8813—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials
    • G01N2030/8818—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials involving amino acids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
    • G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
    • G01N2030/8813—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials
    • G01N2030/8822—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample biological materials involving blood
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2405/00—Assays, e.g. immunoassays or enzyme assays, involving lipids
    • G01N2405/04—Phospholipids, i.e. phosphoglycerides
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/72—Mass spectrometers

Definitions

  • the present invention relates to a solid cancer diagnosis apparatus and a method of providing solid cancer diagnosis information, and more specifically, a solid cancer diagnosis apparatus and lung cancer including lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, stomach cancer, brain tumor, kidney cancer, liver cancer and cervical cancer , Pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, gastric cancer, brain tumor, kidney cancer, liver cancer, and cervical cancer.
  • Cancer is a disease in which cells proliferate indefinitely to interfere with normal cell function. Lung cancer, stomach cancer, breast cancer, colon cancer and ovarian cancer are typical, but can occur in virtually any tissue.
  • Cancer diagnosis in the early days was based on external changes in biological tissues due to the growth of cancer cells, but in recent years, detection of trace amounts of biomolecules present in tissues or cells such as blood, sugar chains, DNA, etc. Diagnosis is being attempted. However, the most commonly used cancer diagnosis method is diagnosis using a tissue sample obtained through a biopsy or an image.
  • biopsy has a drawback that it causes great pain to the patient, is expensive, and takes a long time to diagnose.
  • the patient actually has cancer there is a risk that metastasis of cancer may occur during the biopsy process, and in the case of a region where a tissue sample cannot be obtained through a biopsy, the suspected tissue through surgical operation.
  • An object of the present invention is an apparatus for diagnosing solid cancers including lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, gastric cancer, brain tumor, kidney cancer, liver cancer and cervical cancer with high accuracy and short analysis time, and lung cancer, pancreatic cancer, biliary tract
  • lung cancer, pancreatic cancer, biliary tract To provide a method of providing diagnostic information for solid cancer including cancer, colon cancer, breast cancer, stomach cancer, brain tumor, kidney cancer, liver cancer and cervical cancer.
  • the object of the present invention is a concentration measuring unit for measuring the concentration of each of Acyl-carnitine (AC), Nudifloramide (2PY) and Lysophosphatidylcholine (LPC) from a biological sample;
  • a pre-processing unit pre-processing the measured concentration; It is achieved by including; a diagnostic unit that determines the diagnosis information of cancer by performing a linear discriminant analysis (LDA) using the pretreated concentration.
  • LDA linear discriminant analysis
  • the Acyl-carnitine (AC) includes at least one of Decanoyl-L-carnitine (DC), Hexanoyl-L-carnitine (HC), Octanoyl-L-carnitine (OC) and Palmitoyl-L-carnitine (PC), and ,
  • the Lysophosphatidylcholine (LPC) includes any one of Lysophosphatidylcholine 16:0 (LPC16) and Lysophosphatidylcholine 18:0 (LPC18), and the diagnostic unit is at least one of DC, HC, OC, PC, 2PY, LPC16 and LPC18. Based on the concentration, the concentration is a mass peak area, and a determination unit for determining diagnosis information of cancer by performing a linear discrimination analysis with the mass peak area.
  • the diagnosis unit may determine cancer diagnosis information by performing four arithmetic operations using the pre-processed concentration.
  • the concentration is obtained through a liquid chromatography-mass spectrometer (LC-MS), and the mass spectrometer may be any one of triple TOF, triple quadrupole, and MALDI TOF capable of quantitative measurement.
  • LC-MS liquid chromatography-mass spectrometer
  • the cancer may be any one of solid cancer including lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, stomach cancer, brain tumor, kidney cancer, liver cancer, and cervical cancer.
  • Another object of the present invention is a concentration measuring unit for measuring the concentration of DC from a biological sample;
  • a pretreatment unit pre-treating the measured concentration; It is achieved by including a; diagnosis unit for determining diagnosis information of cancer by performing a linear discrimination analysis using the pre-processed concentration.
  • the DC uses all the measured concentrations, including the measured concentration and the concentration of HC, OC, and PC, and the DC is the measured concentration and the concentration of HC, OC, PC, 2PY, LPC16 and LPC18. It may be to use all the concentrations measured above, including further.
  • the diagnostic unit is based on the concentrations of DC, HC, OC, and PC, and is based on the concentrations of DC, HC, OC, PC, 2PY, LPC16 and LPC18, and the concentration has the mass peak area as a mass peak area. It may include a; determination unit for determining the diagnosis information of the cancer by performing linear discrimination analysis.
  • the diagnosis unit may determine cancer diagnosis information by performing four arithmetic operations using the pre-processed concentration.
  • the concentration is obtained through liquid chromatography-mass spectrometry, and the mass spectrometer may be any one of triple TOF, triple quadrupole, and MALDI TOF capable of quantitative measurement.
  • the cancer may be any one of solid cancer including lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, stomach cancer, brain tumor, kidney cancer, liver cancer, and cervical cancer.
  • an object of the present invention can be achieved by a method of providing information for cancer diagnosis by performing a linear discrimination analysis with at least one of AC, 2PY, and LPC concentrations from a biological sample.
  • the AC may include at least one of DC, HC, OC, and PC
  • the LPC may include any one of LPC16 and LPC18.
  • the concentration may be obtained by mass spectrometry of a biological sample by mass peak area, and the concentration is obtained through a liquid chromatography-mass spectrometer, and the mass spectrometer is any one of Triple TOF, Triple Quadrupole and MALDI TOF capable of quantitative measurement. It can be one.
  • the cancer may be any one of solid cancer including lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, stomach cancer, brain tumor, kidney cancer, liver cancer, and cervical cancer.
  • obtaining the concentrations of DC, HC, OC, PC, 2PY, LPC16, and LPC18 from the biological sample; and pre-treating the measured concentration; and the result of linear discrimination based on the pre-treated DC concentration Cancer was determined based on the results of linear discrimination analysis with the pretreated DC, HC, OC and PC concentrations and the linear discrimination analysis with the pre-treated DC, HC, OC, PC, 2PY, LPC16 and LPC18 concentrations. It may include a step of diagnosing.
  • an apparatus for diagnosing solid cancer including lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, stomach cancer, brain tumor, kidney cancer, liver cancer and cervical cancer with short analysis time and high accuracy, and lung cancer, pancreatic cancer, biliary tract cancer , Colon cancer, breast cancer, gastric cancer, brain tumor, kidney cancer, liver cancer and cervical cancer, including solid cancer diagnostic information is provided.
  • FIG. 1 is a block diagram of a cancer diagnosis apparatus according to an embodiment of the present invention.
  • FIG 3 shows the relative quantitative values of LPC16, LPC18, and 2PY in blood obtained from the cancer patient group and the normal control group.
  • Figure 4 shows the absolute quantification values of DC and OC in plasma obtained from a cancer patient group and a normal control group.
  • the "biological sample” is whole blood, serum, plasma, urine, stool, sputum, saliva, tissue, cells, cells Samples such as extracts, in vitro cell cultures, etc. are included, but are not limited thereto. In the examples described below, serum from a cancer patient group and a normal control group was used as a biological sample.
  • the present invention is based on the discovery that Acyl-carnitine (AC) is useful as a marker for solid cancer including lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, stomach cancer, brain tumor, kidney cancer, liver cancer, and cervical cancer.
  • AC Acyl-carnitine
  • the solid cancer of the present invention may include cervical cancer, esophageal cancer, colon cancer, gastric cancer, hepatocellular carcinoma, and breast cancer determined as solid cancer.
  • the AC includes at least one of Decanoyl-L-carnitine (DC), Hexanoyl-L-carnitine (HC), Octanoyl-L-carnitine (OC), and Palmitoyl-L-carnitine (PC).
  • DC Decanoyl-L-carnitine
  • HC Hexanoyl-L-carnitine
  • OC Octanoyl-L-carnitine
  • PC Palmitoyl-L-carnitine
  • the present invention is based on finding that Nudifloramide (2PY) is useful as a marker for solid cancers including lung cancer, pancreatic cancer, biliary tract cancer and colon cancer.
  • 2PY The official name of 2PY is (N-Methyl-2-pyridoxone-5-carboxamide; 1,6-Dihydro-1-methyl-6-oxonicotinamide; 3-Carbamoyl-1-methyl-6-pyridone), and the structural formula is as follows: same.
  • the present invention is based on the discovery that Lysophosphatidylcholine (LPC) is useful as a marker for solid cancers including lung cancer, pancreatic cancer, biliary tract cancer and colon cancer.
  • LPC Lysophosphatidylcholine
  • the LPC includes any one of Lysophosphatidylcholine 16:0 (LPC16) and Lysophosphatidylcholine 18:0 (LPC18).
  • DC and OC appeared at a generally lower concentration in solid cancer patients including breast cancer, gastric cancer, brain tumor, kidney cancer, liver cancer and cervical cancer (FIG. 4).
  • solid cancer including lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, stomach cancer, brain tumor, kidney cancer, liver cancer and cervical cancer are diagnosed, but the concentration is not limited thereto.
  • Concentration more specifically, can be measured using liquid chromatography-mass spectrometry (LC-MS), and with a mass spectrometer, Triple-TOF, Triple Quadrupole, or MALDI capable of quantitative measurement TOF can be used.
  • LC-MS liquid chromatography-mass spectrometry
  • solid cancer including lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, gastric cancer, brain tumor, kidney cancer, liver cancer, and cervical cancer can be diagnosed using the concentrations of these seven markers. At least one of the concentrations of 4 types of AC, 2PY, and 2 types of LPC may be used.
  • Lung cancer pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, stomach cancer, brain tumor, kidney cancer, liver cancer and cervical cancer by performing a linear discriminant analysis (LDA) using some or all of the concentrations of the seven markers. Determine the solid rock to contain.
  • LDA linear discriminant analysis
  • solid cancer including lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, gastric cancer, brain tumor, kidney cancer, liver cancer and cervical cancer can be diagnosed by measuring only the concentration of the markers and performing linear discrimination analysis. Therefore, solid cancer diagnosis including lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, stomach cancer, brain tumor, kidney cancer, liver cancer and cervical cancer can be quickly performed.
  • FIG. 1 shows a solid cancer diagnosis apparatus including lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, stomach cancer, brain tumor, kidney cancer, liver cancer, and cervical cancer according to an embodiment of the present invention.
  • the solid cancer diagnosis apparatus 1 includes a concentration measuring unit 100, a pretreatment unit 200, and a diagnosis unit 300.
  • the concentration measurement unit 100 acquires mass spectrometry data detected from a biological sample.
  • the mass spectrometry data may include only data for a marker, and the marker may include DC, and may further include at least one of HC, OC, PC, 2PY, LPC16, and LPC18.
  • the mass spectrometric data may be a concentration for a marker (area of a mass peak corresponding to a marker).
  • the pretreatment unit 200 performs preprocessing necessary for the measured mass peak area.
  • the common log value of the mass peak area was taken as a pretreatment, and then the data was transferred to the diagnosis unit.
  • necessary pretreatment may be performed such as multiplying the measured mass peak area by an appropriate scaling factor for normalization or the like.
  • the diagnostic unit 300 performs a linear discrimination analysis using the concentration of the pre-treated markers, and is positive for solid cancer including lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, stomach cancer, brain tumor, kidney cancer, liver cancer, and cervical cancer.
  • solid cancer including lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, stomach cancer, brain tumor, kidney cancer, liver cancer, and cervical cancer.
  • a negative solid cancer including lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, gastric cancer, brain tumor, kidney cancer, liver cancer and cervical cancer is determined.
  • the diagnostic unit 300 uses DC concentration alone, or all four AC concentrations (DC, HC, OC, PC), or four types of AC (DC, HC, OC, PC). ) To the concentration of 2PY, LPC16, and LPC18 may be used.
  • diagnosis unit 300 may determine cancer diagnosis information by performing four arithmetic operations using the concentration of the pre-processed marker.
  • the diagnosis unit 300 uses the pre-treated concentration of the marker, as well as linear discrimination analysis, and also through four arithmetic operations including addition, subtraction, multiplication, and division, for lung cancer, pancreatic cancer, biliary tract cancer, and colon cancer.
  • Breast cancer, gastric cancer, brain tumor, kidney cancer, liver cancer and cervical cancer including solid cancer positive or lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, gastric cancer, brain tumor, kidney cancer, liver cancer and cervical cancer Can judge negative.
  • the diagnostic unit 300 uses DC concentration alone, or all four AC concentrations (DC, HC, OC, PC), or four types of AC (DC, HC, OC, PC). ) To the concentration of 2PY, LPC16, and LPC18 may be used.
  • the solid cancer diagnosis apparatus 1 may further include an output unit notifying the diagnosis result, and the output unit may be a display device or a printer.
  • the solid cancer diagnosis apparatus 1 described above may be variously modified. For example, if there is no necessary pre-processing, the pre-processing unit 200 may be omitted.
  • Example 1 Diagnosis of lung cancer, pancreatic cancer, biliary tract cancer and colon cancer
  • Serum was obtained from 36 normal control subjects, 10 lung cancer patients, 36 biliary tract cancer patients, 36 colon cancer patients, and 36 pancreatic cancer patients.
  • the LC used was Eksigent ultra LC 110-XL system, and the MS was AB Sciex Triple TOF 5600+ system.
  • the MS was equipped with a DuoSpray ion source.
  • the analysis sample was first entered into the analyzer through an Atlantis T3 sentry guard cartridge (3 mm, 2.1 10 mm; Waters) connected to the Eksigent ultraLC 110-XL system, and separated in the Atlantis T3 column (3 mm, 2.1 100 mm; Waters). .
  • the solvent is a two-step linear gradient (solvent A, 0.1% FA in water; solvent B, 100% Acetonitrile; with 1% solvent B for 2min, 1 to 30% B for 6 min, 30 to 90% B for 8 min, 90% B for 4 min, 90 to 1% B for 1 min and 9 min in 1% B) was used.
  • the area of the mass peak having the same mass value was calculated among the mass spectra of the same time period as the time period when metabolites corresponding to 4 types of AC, 2PY, and 2 types of LPC passed through liquid chromatography.
  • FIG. 2 shows the relative quantification values (mass peak area) of four ACs in blood obtained from a cancer patient group and a normal control group.
  • the relative quantification values of HC, OC, DC, and PC in blood were obtained through mass spectrometry.
  • OC and DC are generally present in lower amounts in the blood of patients with lung cancer, pancreatic cancer, biliary tract cancer, and colon cancer compared to HC and PC.
  • FIG. 3 shows the relative quantitative values of LPC16, LPC18, and 2PY in blood obtained from the cancer patient group and the normal control group.
  • the relative quantitative values of LPC16, LPC18, and 2PY in blood were also obtained through mass spectrometry.
  • LPC16 and LPC18 are generally present in lower amounts in the blood of lung cancer, pancreatic cancer, biliary tract cancer, and colon cancer patients compared to the normal control group, and 2PY is higher in the blood of some biliary tract cancer patients and colon cancer patients. It can be seen that it exists.
  • the above [Table 1] relates to the screening ability for each cancer type when a linear discrimination analysis is performed using only the relative quantitative value of DC in blood.
  • the prior probability was considered as the ratio of the number of samples. Even if only the relative quantification of DC in blood was used, the screening ability for each cancer type was very excellent, and in the case of lung cancer, both sensitivity and specificity were measured as 100%.
  • [Table 4] shows the relative quantitative value (mass peak area) of the HC in the blood obtained from the cancer patient group and the normal control group
  • [Table 5] shows the OC of the blood obtained from the cancer patient group and the normal control group.
  • the relative quantification value (mass peak area) is shown
  • the following [Table 6] shows the relative quantification value (mass peak area) of the DC in blood obtained from the cancer patient group and the normal control group
  • the following [Table 7] shows the cancer patient group
  • Figure 2 shows the relative quantitative value (mass peak area) of the PC in the blood obtained from the normal control group and.
  • Table 8 shows the relative quantitative value (mass peak area) of the 2PY in blood obtained from the cancer patient group and the normal control group
  • Table 9 shows the relative quantitative value (mass) of the LPC16 in the blood obtained from the cancer patient group and the normal control group. Peak area
  • Table 10 shows the relative quantitative value (mass peak area) of the LPC18 in blood obtained from the cancer patient group and the normal control group, and is the data of FIG.
  • CTL of Sample Name is a normal control
  • LC lung cancer
  • BDC biliary tract cancer
  • CRC colon cancer
  • PRC colon cancer
  • Example 2 Diagnosis of breast cancer, stomach cancer, brain tumor, kidney cancer, liver cancer and cervical cancer
  • Plasma was obtained from normal controls, breast cancer patients, gastric cancer patients, brain tumor patients, kidney cancer patients, liver cancer patients, and cervical cancer patients, respectively.
  • the LC used was Eksigent ultra LC 110-XL system, and the MS was AB Sciex Triple TOF 5600+ system.
  • the MS was equipped with a DuoSpray ion source.
  • the analysis sample was first entered into the analyzer through an Atlantis T3 sentry guard cartridge (3 mm, 2.1 10 mm; Waters) connected to the Eksigent ultraLC 110-XL system, and separated in the Atlantis T3 column (3 mm, 2.1 100 mm; Waters). .
  • the solvent is a two-step linear gradient (solvent A, 0.1% FA in water; solvent B, 100% Acetonitrile; with 1% solvent B for 2min, 1 to 30% B for 6 min, 30 to 90% B for 8 min, 90% B for 4 min, 90 to 1% B for 1 min and 9 min in 1% B) was used.
  • Tables 11 and 4 show the absolute quantification values of DC and OC in plasma obtained from the cancer patient group and the normal control group.
  • the absolute quantification values of DC and OC in plasma were obtained through mass spectrometry.
  • both DC and OC are present in relatively lower amounts in plasma of breast cancer, gastric cancer, brain tumor, kidney cancer, liver cancer, and cervical cancer patient groups compared to the normal control group.
  • HC Hexanoyl-carnitine
  • PC Palmitoyl-carnitine
  • AC including DC, HC, OC, and PC
  • first and second may be used to describe various components, but the components should not be limited by the terms. These terms are used only for the purpose of distinguishing one component from another component.
  • Spatially relative terms such as below (below, beneath, lower) and above (above, upper) facilitate the correlation between one device or components and other devices or components as shown in the drawing. Can be used to describe. Spatially relative terms should be understood as terms including different directions of the device during use or operation in addition to the directions shown in the drawings. For example, when an element shown in the figure is turned over, an element described below (beneath) another element may be placed above the other element. Accordingly, below, which is an exemplary term, may include both directions below and above. The device may be oriented in other directions, and thus spatially relative terms may be interpreted according to the orientation.
  • the expression indicating a part such as “part” or “part” is a device in which the corresponding component may include a specific function, software that may include a specific function, or a device that may include the function It means that it can represent a combination of software and software, but it cannot be said that it is limited to the expressed function, and this is provided only to help a more general understanding of the present invention, and those with ordinary knowledge in the field to which the present invention belongs If ramen, various modifications and variations are possible from these substrates.
  • the method according to an embodiment of the present invention may be implemented in the form of program instructions that can be executed through various computer means and recorded in a computer-readable medium.
  • the computer-readable medium may include program instructions, data files, data structures, and the like alone or in combination.
  • the program instructions recorded on the medium may be specially designed and configured for the present invention, or may be known and usable to those skilled in computer software.
  • Examples of computer-readable recording media include magnetic media such as hard disks, floppy disks, and magnetic tapes, optical media such as CD-ROMs and DVDs, and magnetic media such as floptical disks.
  • -A hardware device specially configured to store and execute program instructions such as magneto-optical media, and ROM, RAM, flash memory, and the like.
  • Examples of the program instructions include not only machine language codes such as those produced by a compiler, but also high-level language codes that can be executed by a computer using an interpreter or the like.
  • the above-described hardware device may be configured to operate as one or more software modules to perform the operation of the present invention, and vice versa.
  • Embodiments of the invention are used herein to represent the invention, its aspects, its features, its concepts, and/or examples thereof.
  • a physical embodiment of an apparatus, article of manufacture, machine, and/or process embodying the present invention refers to one or more aspects, features, concepts, examples, etc. described with reference to one or more embodiments described herein.
  • embodiments may incorporate the same or similarly named functions, steps, modules, etc., which may use the same or different reference numerals, and as such, the functions, Steps, modules, etc. may be the same or similar functions, steps, modules, etc. or others.
  • the solid cancer diagnosis device including lung cancer, pancreatic cancer, biliary tract cancer, colon cancer, breast cancer, stomach cancer, brain tumor, kidney cancer, liver cancer, and cervical cancer according to the present invention and the method of providing solid cancer diagnosis information, the analysis time is short and the accuracy is high. Solid cancer can be diagnosed.

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